Synthesis of the porcine LH- and FSH-releasing hormone by the solid-phase method

Matsuo, Hisayuki; Arimura, Akira; Nair, R. M. G.; Schally, Andrew V.

doi:10.1016/0006-291x(71)90491-8

Cited by 219 publications

(44 citation statements)

References 10 publications

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“…The availability of synthetic LH-releasing hormone/FSHreleasing hormone (14)(15)(16) opens new possibilities for study of the mechanism of action of this neurohormone in the adenohypophysis. Confirming previous observations made both iF vivo and in vitro (4-8, 10, 13, 42-45) …”

Section: Discussionmentioning

confidence: 99%

“…Adenohypophyseal tissue was first incubated for 60 min at 370 in an atmosphere of 5% C02-95% 02 in 1.0 ml of Krebs Ringer bicarbonate buffer containing 11 mM 1-glucose (KRBG) as described (22 10. method (14) and extensively purified (23). The sample used was homogeneous by thin-layer chromatography and electrophoresis and had maximal biological activity (23).…”

Section: Methodsmentioning

confidence: 99%

“…Since this peptide stimulates the release of both LH and FSH under various experimental conditions (4-8, 10-13), it has been called the LH-releasing hormone/FSH-releasing hormone (4,5,7) or the gonadotropin-releasing factor (12). The availability of synthetic LH-releasing hormone/FSHreleasing hormone (14)(15)(16) and of its analogs is of obvious importance for studies of the mechanism of action of this neurohormone in the adenohypophysis.…”

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confidence: 99%

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Stimulation of Adenosine 3′:5′-Cyclic Monophosphate Accumulation in Anterior Pituitary Gland In Vitro by Synthetic Luteinizing Hormone-Releasing Hormone

Borgeat

Chavancy

Dupont

et al. 1972

Proc. Natl. Acad. Sci. U.S.A.

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183

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A near-maximal dose (20 ng/ml) of synthetic luteinizing hormone(LH)-releasing hormone/follicle-stimulating hormone(FSH)-releasing hormone added to incubated anterior pituitary tissue of male rats leads to concomitant increases of intracellular concentrations of adenosine 3': 5'-monophosphate and of release of both LH and FSH. The stimulatory effect of LH-releasing hormone/ FSH-releasing hormone is observed after a lag period of about 90 min and is progressive at later time intervals; a 3-fold stimulation of cAMP accumulation over control is seen after 210 min of incubation. Half-maximal stimulation of cAMP accumulation is observed between 0.1 and 1.0 ng/ml (0.1-1 nM) of LH-releasing hormone/FSH-releasing hormone. In the presence of 10 mM theophylline, the stimulatory effect of LH-releasing hormone/FSH-releasing hormone on cAMP accumulation is similar to that observed in the absence of the inhibitor of cyclic nucleotide phosphodiesterase, indicating that the releasing hormone exerts its effect by specific activation of adenylate cyclase in LH-and FSH-secreting cells rather than by inhibition of cyclic nucleotide phosphodiesterase. Since the release of growth hormone, thyrotropin, prolactin, and adrenocorticotropic hormone is not affected by LH-releasing hormone/FSH-releasing hormone, and since cAMP stimulates the release of all six adenohypophyseal hormones. the observed changes of cAMP concentrations indicate specific stimulation of adenylate cyclase activity in LHand FSH-secreting cells of the adenohypophysis.Secretion of luteinizing hormone (LH) and of follicle-stimulating hormone (FSH) by the anterior pituitary gland is controlled by a neurohormone released from the hypothalamic area and carried to its specific adenohypophyseal site of action by a portal blood system (1-4). Recently, after more than 10 years of research in many laboratories, this neurohormone was isolated from porcine (5-7) and ovine (8) hypothalami and characterized as a decapeptide having the following structure: (pyro)Glu-His-Try-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2 (9-11). Since this peptide stimulates the release of both LH and FSH under various experimental conditions (4-8, 10-13), it has been called the LH-releasing hormone/FSH-releasing hormone (4, 5, 7) or the gonadotropin-releasing factor (12). The availability of synthetic LH-releasing hormone/FSHreleasing hormone (14-16) and of its analogs is of obvious importance for studies of the mechanism of action of this neurohormone in the adenohypophysis.There was suggestive evidence for a role of adenosine 3': 5'-cyclic monophosphate (cAMP) as a mediator of the action of LH-releasing hormone/FSH-releasing hormone. These studies pertained to reported stimulatory effects of N6,2'.-Odibutyryl cAMP and theophylline (17) (20, 21). However, definitive proof of the role of the adenylate cyclase system as mediator of the action of LH-releasing hormone/FSH-releasing hormone could be obtained only by measurements of adenohypophyseal adenylate cyclase activity or cAMP concentrations under the inf...

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Stimulation of Adenosine 3′:5′-Cyclic Monophosphate Accumulation in Anterior Pituitary Gland In Vitro by Synthetic Luteinizing Hormone-Releasing Hormone

Borgeat

Chavancy

Dupont

et al. 1972

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

183

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“…Ramirez and Sawyer (1965) first reported the fluctuations in hypothalamic luteinizing hormone-releasing factor during the rat estrous cycle even before the LH-RH was identified by Matsuo et al (1971). With the availability of new sensitive radioimmunoassay methods for estimation of LH-RH, a number of investigators have revealed the cyclic changes in the amount of hypothalamic LH-RH during the cyclic changes in the amount of hypothalamic LH-RH during the cycle (Araki et al, 1975;Asai and Wakabayashi, 1975;Saito et al, 1977;Kalra and Kalra, 1977).…”

mentioning

confidence: 99%

Changes in hypothalamic LH-RH content and blood levels of LH-RH, gonadotropin and estradiol during the preovulatory stage of rat estrous cycle.

Oshima¹,

Morishita

Omura³

et al. 1978

Endocrinol Japon

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SynopsisIn order to investigate the sequence of events concerning gonadotropin surge, serum LH, FSH and estradiol concentrations were measured during the rat estrous cycle as well as hypothalamic and blood levels of LH-RH in the preovulatory stage. Normally cyclic female Wistar rats kept on 12 hr light (from 22.00 hr to 10.00 hr) and 12 hr dark were killed at different times of day during each stage of the cycle. The hypothalamus was quickly dissected out, divided into 3 portions (the anterior, middle and posterior) and extracted in 90% methanol.Blood LH-RH was extracted by affinity chromatography prior to radioimmunoassay.The content of LH-RH in the anterior and middle hypothalamus started to decrease between 1.00hr-3.00hr, reached its nadir at 6.00hr on proestrus and recovered to its previous values on estrus. Almost simultaneously blood LH-RH concentration showed an increase of 18.3 pg/ml-8.8 pg/ml between 1.00hr-3.00hr, and then fell to<1.0pg/ml at 6.00 hr. On the other hand, serum estradiol level began to elevate on diestrus II followed by its peak at 6.00hr on proestrus, while the peaks of serum LH and FSH were observed at 8.00 hr and 10.00hr, respectively.These studies indicate that the elevation of serum estradiol was followed by the release of LH-RH from the hypothalamus and the LH-RH may be responsible for the preovulatory discharge of gonadotropin.

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“…Since the isolation, purification, characterization and synthesis of porcine LHand FSH-releasing hormone (Matsuo, Arimura, Nair & Schally, 1971 ; Schally, Kastin & Arimura, 1971), many investigators (see White, Hedlund, Rippel, Arnold & Flouret, 1973) have successfully synthesized this decapeptide. Potent analogues of this decapeptide have also been synthesized and their potencies compared to that of synthetic LH-RH with respect to hypophysial LH-and FSH-release (Coy & co-authors, 1974;Kastin & co-authors, 1974;Arimura, Vilchez-Martinez & Schally, 1974a; Coy, Coy, Hirotsu & Schally, 1974b) and ovulation-inducing activity in rats (Fujino & co-authors, 1974a, b).…”

Section: Introductionmentioning

confidence: 99%

Ovulation Induction and Antifertility Effects of an Lh-Rh Analogue (Ay-25,205) in Cyclic Rats

Banik¹,

Givner²

1975

Reproduction

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Synthesis of the porcine LH- and FSH-releasing hormone by the solid-phase method

Cited by 219 publications

References 10 publications

Stimulation of Adenosine 3′:5′-Cyclic Monophosphate Accumulation in Anterior Pituitary Gland In Vitro by Synthetic Luteinizing Hormone-Releasing Hormone

Stimulation of Adenosine 3′:5′-Cyclic Monophosphate Accumulation in Anterior Pituitary Gland In Vitro by Synthetic Luteinizing Hormone-Releasing Hormone

Changes in hypothalamic LH-RH content and blood levels of LH-RH, gonadotropin and estradiol during the preovulatory stage of rat estrous cycle.

Ovulation Induction and Antifertility Effects of an Lh-Rh Analogue (Ay-25,205) in Cyclic Rats

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